The overall goal is to develop appropriate and practicable animal models of mental deficiency and other functional deficits associated with congenital defects of the brain in man. The purpose of developing these models is to make possible more effective screening of substances that may produce similar defects in man, as well as to permit analysis of anatomic, pathologic, biochemical, and physiological changes associated with (and presumably causative of) mental deficiency. Specific aims of this project are to determine the behavioral, neuroanatomical, and neurochemical changes associated with a variety of brain malformations we have produced in the ferret by treatment with methylazoxymethanol acetate on different days of gestation. The immediate research goals include: (1) testing ferrets with micrencephaly, lissencephaly, and cerebellar dysplasia on various behavioral tasks; (2) making a systematic anatomic analysis (with Nissl and Golgi stains) of the different brain malformations; (3) producing regional graded brain malformations; (4) neurochemical analyses of normal and treated ferret brains.